Self-Assembled Micelles Prepared From Amphiphilic Dextran-Polylactide Diblock Copolymers for Antitumor Drug Release

Fully biobased diblock copolymers were synthesized by reducing amination from dextran (DEX) and amino-terminated polylactide (PLA). The resulting copolymers were characterized by using nuclear magnetic resonance, Fourier-transform infrared spectroscopy, gel permeation chromatography, and the Kaiser test. Self-assembled copolymer micelles were characterized by transmission electron microscopy and dynamic light scattering. The micelles are spherical in shape, and the particle size increases with the increase of both DEX and PLA block lengths. The critical micellar concentration (CMC) of copolymers was determined by fluorescence spectrometry. Data showed that the CMC decreases with the increase of PLA block length. Drug loading and drug release properties of DEX-PLA micelles were evaluated using curcumin as a model drug. An increase in drug loading content is obtained with the increase of the PLA block length. In vitro drug release from DEX-PLA micelles was performed at 37°C in phosphate-buffered saline. Biphasic release was observed with an initial burst followed by slower release. The drug release rate from DEX-PLA micelles was mainly related to copolymer composition and reached 84.17% at 120 h for the copolymer with the highest hydrophilic/hydrophobic ratio (DEX_10K-PLA₂₀). DEX-PLA micelles present good cytocompatibility as evidenced by the MTT assay, and drug-loaded micelles exhibit significant cytotoxicity to HeLa cells. The half-maximum inhibitory concentration (IC₅₀) of drug-loaded DEX_10K-PLA₂₀ micelles was 9.12 μg/mL, which was lower than that of free curcumin (11.9 μg/mL). Therefore, self-assembled micelles prepared from fully biobased DEX-PLA copolymers could be a promising nanocarrier for hydrophobic antitumor drugs.